Liver has a remarkable capacity to regenerate. After partial hepatectomy or physical, chemical injury, liver starts to regenerate until the liver mass reaches to correct size. Liver regeneration is associated with many liver diseases, such as liver cirrhosis and acute/chronic hepatitis. The progression of hepatocellular carcinoma often accompanies with liver regeneration. Meanwhile, liver regeneration is also implied in partial liver transplantation and hepatocyte transplantation in clinical use.
Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world. China is a high-incidence area of HCC. It is estimated to cause approximately 250,000 deaths annually worldwide, 40% of which is in China (Shaobai Li. “Hepatology”, People's Medical Publishing House, 2002). Because of its high fatality, the incidence and mortality rates are almost equal. The major factors to cause HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, alcoholic cirrhosis and exposure to hepatotoxins like aflatoxin in food and water supplies. Recent studies suggest that the progression of HCC and liver regeneration are closely related: Liver regeneration is a well-regulated hepatocyte proliferation in normal situation, but becomes out of control in HCC. Some hypothesis suggests that process of HCC progression is as follows: liver injury caused by virus infection or toxic chemicals leads to the consequent liver regeneration; chronic injury causes the whole process recur many times and finally becomes out of control, and in the end results in HCC. Thus, understanding the relationship between HCC and liver regeneration will help us to predict and provide treatment for early hepatocellular carcinoma.
Nowadays, the most efficient way to treat several liver diseases is liver transplantation, whose technique is well established. However, the number of donor organs and the problem of immune exclusion inherently limit liver transplantation at present time. Main methods to resolve these two problems are partial liver transplantation and hepatocyte transplantation. Partial liver transplantation enables one donor liver to transplant into two or more patients and gives chance to transplant liver between relatives in order to reduce the immune exclusion. Another optimizing way is hepatocyte transplantation, which is to directly transplant hepatocytes into liver or spleen of patients. The transplanted hepatocytes then integrate into the recipient organs, begin to re-proliferate and perform the function of liver. Hepatocyte transplantation can use hepatocytes from the patients themselves in order to avoid immune exclusion. Both methods utilize the regenerative capacity of liver, but the protein factors essential to liver regeneration and the mechanism of liver regeneration are still unknown.
To meet the needs of liver transplantation and HCC treatment, There is an urgent need in the art to know the factors related to liver regeneration, especially the genes and proteins associated with liver regeneration.